Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance

• Published in: The Journal of immunology (1950) 2017-07, Vol.199 (1), p.119-128
• Main Authors: Yang, Hui, Guo, He-Zhou, Li, Xian-Yang, Lin, Jian, Zhang, Wu, Zhao, Jun-Mei, Zhang, Hong-Xin, Chen, Sai-Juan, Chen, Zhu, Zhu, Jiang
• Format: Article
• Language: English
• Subjects: Animals; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cell Differentiation; Colitis; Colitis - chemically induced; Colitis - immunology; DEAD Box Protein 58 - metabolism; Helper cells; Immunoregulation; Innate immunity; Janus kinase; Janus Kinase 1 - metabolism; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Mice; Ribonucleic acid; RNA; RNA, Viral - immunology; Signal Transduction; Stat3 protein; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - immunology; STAT3 Transcription Factor - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - physiology; Th17 Cells - immunology; Th17 Cells - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1700366

Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4 T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of CD4 T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance. Mechanistically, apo-Rig-I physically associates with Stat3, thereby inhibiting Jak1's association with Stat3 while facilitating Shp2's association to inhibit p-Stat3 levels. Interestingly, inhibition of Stat3 ameliorates the Treg/Th17 imbalance and the colitis observed in mice. Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance.